EP0182520B2 - Gerät zur iontophoretischen Verabreichung von Medikamenten - Google Patents

Gerät zur iontophoretischen Verabreichung von Medikamenten Download PDF

Info

Publication number
EP0182520B2
EP0182520B2 EP19850307771 EP85307771A EP0182520B2 EP 0182520 B2 EP0182520 B2 EP 0182520B2 EP 19850307771 EP19850307771 EP 19850307771 EP 85307771 A EP85307771 A EP 85307771A EP 0182520 B2 EP0182520 B2 EP 0182520B2
Authority
EP
European Patent Office
Prior art keywords
species
drug
assembly
source
electrode member
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP19850307771
Other languages
English (en)
French (fr)
Other versions
EP0182520A2 (de
EP0182520B1 (de
EP0182520A3 (en
Inventor
Darrel F. Unterecker
Joseph B. Phipps
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alza Corp
Original Assignee
Alza Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27099269&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP0182520(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from US06/665,699 external-priority patent/US4747819A/en
Priority claimed from US06/665,698 external-priority patent/US4744787A/en
Application filed by Alza Corp filed Critical Alza Corp
Publication of EP0182520A2 publication Critical patent/EP0182520A2/de
Publication of EP0182520A3 publication Critical patent/EP0182520A3/en
Publication of EP0182520B1 publication Critical patent/EP0182520B1/de
Application granted granted Critical
Publication of EP0182520B2 publication Critical patent/EP0182520B2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0432—Anode and cathode
    • A61N1/0436—Material of the electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0448—Drug reservoir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0444—Membrane

Definitions

  • This invention relates to improvements in iontophoretic drug delivery, particularly to iontophoretic drug delivery apparatus for transdermal medicament delivery and to improvements therein. More specifically, this invention relates to improved apparatus for active (as opposed to passive) transdermal, ambulatory, drug delivery. Yet more particularly, this invention relates to increased efficiency iontophoresis devices or appliances.
  • Iontophoresis according to Dorland's Illustrated Medical Dictionary, is defined to be "the introduction, by means of electric current, of ions of soluble salts into the tissues of the body for therapeutic purposes.” Iontophoretic devices have been known since the early 1900's. GB-A-410,009(1934) describes an iontophoretic device which overcame one of the disadvantages of such early devices known to the art at that time, namely the requirement of a special low tension (low voltage) source of current which meant that the patient needed to be immobilized near such a source.
  • low tension low voltage
  • the device of that British specification was made by forming from the electrodes and the material containing the medicament or drug to be delivered transdermally, a galvanic cell which itself produced the current necessary for iontophoretically delivering the medicament. This ambulatory device thus permitted iontophoretic drug delivery with substantially less interference with the patient's daily occupation.
  • iontophoresis process has been found to be useful in the transdermal administration or introduction of medicaments or drugs including lidocaine hydrochloride, hydrocortisone, acetic acid, fluoride, penicillin, dexamethasone sodium phosphate and many other drugs.
  • lidocaine hydrochloride hydrocortisone
  • acetic acid fluoride
  • fluoride penicillin
  • dexamethasone sodium phosphate and many other drugs.
  • the pilocarpine nitrate stimulates sweat production; the sweat is collected and analyzed for its chloride content to detect the presence of the disease.
  • the active electrode is the electrode from which the ionic substance, medicament, drug precursor or drug (hereinafter “the ionic drug species”) is delivered or driven into the body by electrical repulsion.
  • the other electrode called the indifferent or ground electrode, serves to close the electrical circuit through the body.
  • the circuit is completed by connection of the electrodes to a source of electrical energy, e.g. a battery or appropriately modified household current.
  • the positive electrode (the anoide) will be the active electrode and the negative electrode (the cathode) will serve to complete the circuit.
  • the negative electrode will be the active electrode and the positive electrode will be the indifferent electrode.
  • existing iontophoresis devices generally require a reservoir or source of the ionized or ionizable species (or a precursor of such species) - ie the ionic drug species - which is to be iontophoretically delivered or introduced into the body.
  • reservoirs or sources of ionized or ionizable species include a pouch as described in the previously mentioned Jacobsen US-A-4,250,878, or the pre-formed gel body of US-A-4,383,529 (Webster).
  • Such drug reservoirs when electrically connected to the anode or the cathode of an iontophoresis device to provide a fixed or renewable source of one or more desired species, are generally used with anodes or cathodes which are substantially electrochemically inert. As is more fully discussed below, utilization of such substantially inert electrodes as contemplated in the prior art generally has significant disadvantages.
  • the present invention provides an iontophoretic drug delivery apparatus as defined in claim 1.
  • an iontophoretic drug delivery electrode assembly as defined in claim 4.
  • the present invention provides an iontrophoretic drug delivery electrode assembly as defined in claim 12.
  • the electrode assembly of the apparatus includes a component which is electrochemically active during iontophoretic drug delivery to produce a first species which, with a second species employed in or generated during the operation of said apparatus, is capable of interacting to produce a product which is not sufficiently influenced by electrical fields to be iontophoretically introduced.
  • the present invention permits a method of iontophoretic drug delivery wherein the drug to be iontophoretically delivered, an electrochemically active component of the drug delivery apparatus, or both, are selected so that during operation of the device, the production of unwanted ionic species may be minimized.
  • the drug to be iontophoretically delivered, an electrochemically active component of the apparatus or both are selected to reduce the formation of unwanted water electrolysis products during operation of the device.
  • an electrochemically active component of an iontophoresis device is a part of the device which is oxidized or reduced during iontophoretic drug delivery or which oxidizes or reduces other available species.
  • the electrochemically active component is an electrical current distribution member of the apparatus
  • the improved electrode of this invention provides an iontophoretic device which exhibits enhanced coulombic efficiency in drug delivery processes.
  • the electrode assembly conveniently comprises a reservoir containing the medicament to be iontophoretically delivered, the reservoir being in electrical connection with an electrochemically active component, e.g. an active current distribution member, the species produced from the electrochemically active component during operation of the device interacting with the medicament of the reservoir during iontophoretic drug delivery so as to minimize the formation and delivery of undesired species, the electrochemically active component being in further electrical connection with a source of electrical energy.
  • the electrode assembly includes means for securing the assembly to skin so as to permit iontophoretic drug delivery therefrom.
  • the apparatus of the present invention enables a method of iontophoretic drug delivery having enhanced coulombic efficiency to be performed, the method comprising: selecting the ionic species (e.g. a drug) to be iontophoreticaly delivered, incorporating the ionic species into an electrode assembly (e.g. in its medicament reservoir); selecting the composition or construction of either the anode or the cathode of the iontophoresis apparatus to include an electrochemically active component so that the electrochemical reaction at the anode or the cathode produces species which interact with the ionic species so as to reduce the formation of undesired ions; placing the selected anode or cathode in electrical connection with the ionic species (e.g. in connection with the reservoir) and with a source of electrical energy; and transdermally delivering the selected ionic species into the body while minimizing the formation and transdermal delivery of undesired ions.
  • the ionic species e.g. a drug
  • an electrode assembly e
  • the genesis of the present invention lay in the realization that known iontophoretic drug delivery processes have an efficiency in the range of about 5% or less and that iontophoretic drug delivery is largely a diffusion dependent process. This means that approximately 95% of the current utilized in known iontophoresis processes is consumed in activities other than delivering the intended drug. For example, much current is wasted by the migration of highly mobile species such as H + , OH - , Na + and Cl - .
  • iontophoretic drug delivery efficiency would be enhanced if the availability of species which are more mobile than the drug which was to be delivered were minimized. Minimization of the concentration or charge of species which were more easily transported than the intended species (i.e. a drug) is utilized herein to provide enhanced drug delivery.
  • the enhanced drug delivery described herein may permit iontophoresis to become a viable alternative to other drug delivery techniques.
  • Prior art iontophoretic devices often utilize substantially inert stainless steel, nickel or other nickel and iron alloys as current distribution members or electrodes.
  • electrolysis of water occurs.
  • Hydronium (H + ) ions are formed at the anode and hydroxide ions (OH - ) are produced at the cathode.
  • gaseous hydrogen and oxygen are evolved at the cathode and anode, respectively.
  • nickel or nickel-containing alloys e.g. stainless steel, also occasionally results in the formation of nickel ions at the anode. The nickel ions are then free to migrate into the drug reservoir of the device and from there into the body.
  • Iontophoretic devices which employ such essentially inert electrodes have several inherent disadvantages. First, they exhibit reduced coulombic efficiency of drug transfer (i.e. of charged species) due to the formation of highly mobile hydronium and hydroxide ions at the electrodes. In addition, such devices may evidence instability of pH in the anodic and cathodic reservoirs and adjacent the skin due to the formation of hydronium or hydroxide ions and gaseous products (hydrogen and oxygen) at the electrodes. Lastly, as noted above, while prior art iontophoretic electrodes are substantially electrochemically inert, some undesirable oxidation, e.g. of nickel or other alloy metals, does occur.
  • One method contemplated by the present invention for reducing the formation of undesirable or undesired hydronium ions at an electrode and to reduce contamination of the drug reservoir due to the oxidation of electrode metal is to select intentionally an electrode (e.g. an anode) comprising an electrochemically active or sacrificial component as defined is anyone of the claims which, when oxidized or reduced during operation of the device, produces a species which immediately reacts with ions (e.g. anions) present in the electrode assembly or available to the electrode, e.g.
  • Electrochemically active means “sacrificial” as defined above, but includes a material that is not itself oxidized or reduced but which participates in oxidation / reduction.
  • the anion or cation present in the drug reservoir can be present as a separately added material or as the counter-ion to an ionic or cationic drug species to be delivered.
  • Ferro and ferricyanides of many metals are insoluble and therefore combination of these metals with ion cyanide doped reservoirs may provide suitable sacrificial anode/drug reservoir systems.
  • One aspect of the invention is to employ D x Fe(CN) 6 (x is an integer greater than 0) where it is desired to transport a drug (D+) species through the skin without cationic competition.
  • negatively charged, anionic drug species may be more efficiently delivered if an electrochemically active component of the cathode is intentionally selected utilizing the precepts of this invention.
  • An example of a sacrificial cathode electrochemically active material of this invention is chloridized silver.
  • the AgCl on the surface of a silver cathode is decomposed to give silver metal and chloride anion (AgCl+ e - ⁇ Ag + Cl - ).
  • the chloride anion is free to migrate, along with any anionic drug, into the body.
  • the Ag/AgCl sacrifical cathode is less efficient than the silver/chloride sacrificial in that chloride ion is produced and is delivered to the body.
  • the beneficial aspects of the Ag/AgCl cathode include (a) no hydrogen gas formation and (b) no hydroxyl anions produced at the cathode.
  • a sacrificial cathode of this generic type generally comprises a metallic salt in contact with a metal cathode. Furthermore, device operation must result in the decomposition fo the metallic salt to form a metal in reduced form plus an anion. If both these conditions are met, in this practice of the present invention anionic drugs are delivered with mitigation of pH changes.
  • An example of an anionic drug (D - ) which could be intentionally selected for use with an Ag/AgCl cathode (these drugs would likely to dispersed or dissolved in the ion drug reservoir) is silver salicylate.
  • chloride ions formed at the cathode are free to react with silver or copper ions in the drug reservoir to form an insoluble salt thus allowing the negatively charged D - anion to migrate in to the body without anionic competition.
  • an intercalation-type cathode or anode is employed.
  • Intercalation electrodes have the property of being capable of reducing alkali metal ions, e.g. sodium and potassium.
  • the use of intercalation-type cathode or anode materials is particularly advantageous in that the formation of hydroxyl and hydronium ion is minimized along with a decline in the production of hydrogen or oxygen gas.
  • electrodes comprising intercalation-type materials may be used either on the anode or the cathode of the iontophoresis device and thus can deliver either positively or negatively charged drugs.
  • This can be illustrated for sodium tungstate where the anodic reaction would be: Na 1+x WO 3 ⁇ Na + + Na x WO 3 + e -
  • Na + + Na x WO 3 + e - ⁇ Na 1+x WO 3 For a cathodic reaction, Na + + Na x WO 3 + e - ⁇ Na 1+x WO 3 .
  • an amalgam electrode is employed optionally in conjunction with the addition of specific metal cations to the drug reservoir, e.g. optionally with selection of a drug having a specific metal cation.
  • the amalgam electrode is consumed during electrochemical discharge of the apparatus, and it reacts with a species intentionally made available to the electochemical oxidation /reduction product of the amalgam, e.g. by adding a selected drug to the system such as in the drug reservoir.
  • the amalgam material herein described is electrochemically reacted and undesired, highly mobile, charged species are consumed or removed.
  • the production of hydroxyl and hydronium ions during electrochemical discharge also is reduced. Again pH stability is obtained, thus increasing the overall stability and efficiency of the drug delivery device.
  • the counteranion is preferably either a metal ion which in the redox conditions of the electrode assembly can plate onto or be absorbed into the cathode or an anion which reacts with cations generated at the cathode to produce a neutral species (eg water, a solid precipitate, or a neutral complex), or an ionic species of relatively low susceptibility to iontophoretic delivery from the electrode assembly.
  • a neutral species eg water, a solid precipitate, or a neutral complex
  • its countercation is preferably such as to react with anions generated at the anode to produce a neutral species or an ionic species of relatively low susceptibility to iontophoretic delivery from the electrode assembly.
  • Figure 1 is a cross sectional view of one embodiment of the electrode assembly of the apparatus of the invention.
  • FIG 1 there is depicted, schematically, in cross section, a single substantially disc-like electrode assembly 10 which is intended for use in an iontophoretic drug delivery apparatus. It is to be understood that electrode assembly 10 is but one of the two electrodes necessary for successful operation of an iontophoresis device and that the source of electrical energy that may also be required is also not depicted in Figure 1.
  • electrode assembly 10 comprises a support or housing 12 which is generally "U" shaped in cross section and which is preferably flexible.
  • the support 12 is preferably a flexible backing member, conveniently substantially flat in form.
  • Support 12 may be produced from self-supporting polymeric foam.
  • Perimeter surface 14 of housing 12 would optionally have disposed thereon a skin-compatible, pressure-sensitive, biomedical adhesive 16 which is intended to hold the electrode in place on the patient's skin during iontophoretic drug delivery.
  • the iontophoresis device may be held in place by other means, e.g a strap, in which instance adhesive 16 would not be needed.
  • electrode assembly 10 contemplates drug delivery generally in the direction which appears as downwards in the Figure.
  • a drug reservoir 18, which in the illustrated embodiment of the invention is a gel or gel matrix 21 containing the ionic drug species 19 which is to be transdermally introduced across the skin barrier.
  • the self-supporting, skin-compatible gel matrix 21 for the drug would contain sufficient drug 19 so that approximately a one molar solution (applying the definition of a molarity from solvent-solute interactions) would result.
  • Drug concentrations (in the reservoir) in the range of 0.02M to 1.0M or more can conveniently be employed in the practice of this invention.
  • the lower reservoir drug concentration ranges e.g. less than about 0.5 molar) can be used in the efficient devices described herein.
  • any of a number of possible gel matrices may be employed, those being described in the previously mentioned Webster patent comprising a particularly preferred practice of this invention.
  • Agar or polyvinylpyrrolidone gels also are advantageously employed herein.
  • Exterior connector 20 which in this embodiment is a wire. Exterior connector 20 is in further electrical contact with a current distribution member comprising a tab or plate 23 in electrical contact with an optional screen 22.
  • the current distribution member would comprise silver. (The current distribution member need not be pure silver. An exterior layer of silver is all that is needed.) The silver screen is optionally included only to increase the surface area of the current distribution member.
  • an external source of electrical energy may be connected to exterior connector 20 which is, in turn, electrically connected to the silver current distribution member 22, 23.
  • Electrode assembly 10 would be placed in contact with a patient's skin and pressed with sufficient firmness so that pressure sensitive adhesive 16 would hold the drug reservoir 18 in contact therewith by means of flexible housing 12.
  • Silver tab 20 would be electrically connected to a source of electrical energy, preferably a small battery. Utilization of a battery permits iontophoretic drug delivery without substantial interference with the normal activities of the patient.
  • stationary electrical supply sources be employed in which case it would likely be necessary for the patient to be substantially immobilised.
  • a second indifferent or cooperating electrode would then be placed in contact with the patient's skin at a site separate from but electrically adjacent to the site on which electrode assembly 10 has been placed. Upon connection to a source of electrical energy, migration of charged species from reservoir 18 would occur.

Landscapes

  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Biomedical Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Electrotherapy Devices (AREA)
  • Medicinal Preparation (AREA)

Claims (16)

  1. Vorrichtung zur iontophoretischen Verabreichung von Medikamenten mit einer Elektrodenanordnung (10) zur iontophoretischen Verabreichung von Medikamenten, die selbst ein Elektrodenelement (22, 23) in elektrisch leitender Verbindung mit einer Source (18, 19, 21) für ein iontophoretisch zu verabreichendes, ionisches Medikament und für die Gegenionen davon umfasst,
    wobei die Anordnung wenigstens eine elektrochemisch aktive Komponente, die während der iontophoretischen Verabreichung des Medikaments oxidiert oder reduziert wird,
    oder die andere verfügbare Spezies oxidiert oder reduziert, in elektrisch leitender Verbindung mit der Source enthält, und
    wobei wenigstens eine der elektrochemisch aktiven Komponenten und die Gegenionen so gewählt sind, dass bei Betätigung der Anordnung die Erzeugung ionischer Spezies an dem Elektrodenelement im wesentlichen vermieden wird oder die an dem Elektrodenelement erzeugten ionischen Spezies im wesentlichen vollständig durch in oder bei der Source vorliegende oder gebildete Spezies und/oder durch die elektrochemisch aktive Komponente in Spezies umgewandelt werden, die eine niedrigere Suszeptibilität für eine iontophoretische Abgabe durch die Vorrichtung aufweisen, dadurch gekennzeichnet, dass die Anordnung als die elektrochemisch aktive Komponente das Elektrodenelement (22, 23) enthält, das eine Kathode ist, die aus Silberchlorid in Kontakt mit Silber ist,
    die Gegenionen für die ionische Medikamentenspezies (19), welche in der Source vorliegen, Silberionen enthalten,
    und die Source ein Gelreservoir umfasst, in der das iontophoretisch abzuscheidende Medikament enthalten ist,
    wobei bei Betätigung der Anordnung eine Wasserelektrolyse an dem Elektrodenelement im wesentlichen vermieden wird.
  2. Vorrichtung nach Anspruch 1, die weiterhin Haltemittel (12) zum Halten der Source und/oder des Elektrodenelements umfasst.
  3. Vorrichtung nach Anspruch 1 oder 2, worin das Medikament in dem Gel in einer Konzentration von weniger als 0,5 molar enthalten ist.
  4. Elektrodenanordnung (10) zur iontophoretischen Verabreichung von Medikamenten, umfassend eine Elektrodenelement (22, 23) in elektrisch leitender Verbindung mit einer Source (18, 19, 21) für ein iontophoretisch zu verabreichendes, ionisches Medikament und für die Gegenionen davon,
    wobei die Anordnung wenigstens eine elektrochemisch aktive Komponente, die während der iontophoretischen Verabreichung des Medikaments oxidiert oder reduziert wird,
    oder die andere verfügbare Spezies oxidiert oder reduziert, in elektrisch leitender Verbindung mit der Source enthält, und
    wobei wenigstens eine der elektrochemisch aktiven Komponenten und die Gegenionen so gewählt sind, dass bei Betätigung der Anordnung die Erzeugung ionischer Spezies an dem Elektrodenelement im wesentlichen vermieden wird oder die an dem Elektrodenelement erzeugten ionischen Spezies im wesentlichen vollständig durch in oder bei der Source vorliegende oder gebildete Spezies und/oder durch die elektrochemisch aktive Komponente in Spezies umgewandelt werden, die eine niedrigere Suszeptibilität für eine iontophoretische Abgabe durch die Vorrichtung aufweisen, dadurch gekennzeichnet, dass
    die Anordnung als die elektrochemisch aktive Komponente das Elektrodenelement (22, 23) enthält, das aus einer Einlagerungsverbindung oder Amalgam ist,
    wobei bei Betätigung der Anordnung eine Wasserelektrolyse an dem Elektrodenelement im wesentlichen vermieden wird.
  5. Vorrichtung zur iontophoretischen Verabreichung von Medikamenten mit einer Elektrodenanordnung (10) nach Anspruch 4.
  6. Vorrichtung nach Anspruch 5, welche weiterhin Haltemittel (12) zum Halten der Source und/oder des Elektrodenelements umfasst.
  7. Vorrichtung nach Anspruch 5 oder 6, worin die Source ein Gelreservoir umfasst, in der das iontophoretisch abzuscheidende, ionische Medikament enthalten ist.
  8. Vorrichtung nach Anspruch 7, worin das Medikament in dem Gel in einer Konzentration von weniger als 0,5 molar enthalten ist.
  9. Vorrichtung nach Anspruch 7 oder 8, worin die Gegenionen Alkalimetallionen enthalten.
  10. Vorrichtung nach einem der Ansprüche 7 bis 9, worin die Einlagerungsverbindung eine Einlagerung eines Materials, ausgewählt unter Natriumwolframat, Natriumvanadat (NaV6O3) und Graphit, ist.
  11. Vorrichtung nach einem der Ansprüche 7 bis 9, worin das Amalgam Quecksilber/Cadmiumamalgam ist.
  12. Elektrodenanordnung (10) zur iontophoretischen Verabreichung von Medikamenten, umfassend
    ein Elektrodenelement (22, 23) in elektrisch leitender Verbindung mit einer Source (18, 19, 21) für ein ionthophoretisch zu verabreichendes, ionisches Medikament und für die Gegenionen davon,
    wobei die Anordnung wenigstens eine elektrochemisch aktive Komponente, die während der iontophoretischen Verabreichung des Medikaments oxidiert oder reduziert wird,
    oder die andere verfügbare Spezies oxidiert oder reduziert, in elektrisch leitender Verbindung mit der Source enthält, und
    wobei wenigstens eine der elektrochemisch aktiven Komponenten und die Gegenionen so gewählt sind, dass bei Betätigung der Anordnung die Erzeugung ionischer Spezies an dem Elektrodenelement im wesentlichen vermieden wird oder die an dem Elektrodenelement erzeugten ionischen Spezies im wesentlichen vollständig durch in oder bei der Source vorliegende oder gebildete Spezies und/oder durch die elektrochemisch aktive Komponente in Spezies umgewandelt werden, die eine niedrigere Suszeptibilität für eine iontophoretische Abgabe durch die Vorrichtung aufweisen, dadurch gekennzeichnet, dass die Anordnung als die elektrochemisch aktive Komponente das Elektrodenelement (22, 23) enthält, das eine Silber-, Zinn-, Nickel- oder Mangan-Anode ist,
    und die Medikamentengegenionen Ferrocyanid- oder Ferricyanidionen enthalten,
    wobei bei Betätigung der Anordnung eine Wasserelektrolyse an dem Elektrodenelement im wesentlichen vermieden wird.
  13. Vorrichtung zur iontophoretischen Verabreichung von Medikamenten, umfassend eine Elektrodenanordnung (10) nach Anspruch 12.
  14. Vorrichtung nach Anspruch 13, welche weiterhin Haltemittel (12) zum Halten der Source und/oder des Elektrodenelements umfasst.
  15. Vorrichtung nach Anspruch 13 oder 14, worin die Source ein Gelreservoir umfasst, in der das iontophoretisch abzuscheidende, ionische Medikament enthalten ist.
  16. Vorrichtung nach Anspruch 15, worin das Medikament in dem Gel in einer Konzentration von weniger als 0,5 molar enthalten ist.
EP19850307771 1984-10-29 1985-10-28 Gerät zur iontophoretischen Verabreichung von Medikamenten Expired - Lifetime EP0182520B2 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US06/665,699 US4747819A (en) 1984-10-29 1984-10-29 Iontophoretic drug delivery
US665699 1984-10-29
US665698 1984-10-29
US06/665,698 US4744787A (en) 1984-10-29 1984-10-29 Iontophoresis apparatus and methods of producing same

Publications (4)

Publication Number Publication Date
EP0182520A2 EP0182520A2 (de) 1986-05-28
EP0182520A3 EP0182520A3 (en) 1987-09-02
EP0182520B1 EP0182520B1 (de) 1992-03-25
EP0182520B2 true EP0182520B2 (de) 2002-08-28

Family

ID=27099269

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19850307771 Expired - Lifetime EP0182520B2 (de) 1984-10-29 1985-10-28 Gerät zur iontophoretischen Verabreichung von Medikamenten

Country Status (4)

Country Link
EP (1) EP0182520B2 (de)
JP (1) JP2584438B2 (de)
CA (1) CA1267937A (de)
DE (1) DE3585722D1 (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5135477A (en) * 1984-10-29 1992-08-04 Medtronic, Inc. Iontophoretic drug delivery
US4722726A (en) * 1986-02-12 1988-02-02 Key Pharmaceuticals, Inc. Method and apparatus for iontophoretic drug delivery
US4886489A (en) * 1986-03-19 1989-12-12 Jacobsen Stephen C Flow-through methods and apparatus for iontophoresis application of medicaments at a controlled pH
JPS62268570A (ja) * 1986-05-19 1987-11-21 株式会社アドバンス イオントフオレ−ゼ用電極
EP0318776A1 (de) * 1987-12-04 1989-06-07 Robert Tapper Verfahren und Gerät zur Verminderung des Hautverletzung bei Gebrauch von Elektroden
US5084008A (en) * 1989-12-22 1992-01-28 Medtronic, Inc. Iontophoresis electrode
JP3740549B2 (ja) * 1990-03-30 2006-02-01 アルザ・コーポレーション イオン侵透療法による薬剤投与の装置と方法
CA2079315C (en) * 1990-03-30 2003-04-15 Joseph Bradley Phipps Device and method for iontophoretic drug delivery
FR2687321B1 (fr) * 1992-02-14 1999-04-16 Elf Aquitaine Dispositif d'ionophorese pour l'administration transcutanee d'une quantite totale donnee d'un principe actif a un sujet.
WO1995027530A1 (en) * 1994-04-08 1995-10-19 Alza Corporation Electrotransport system with ion exchange competitive ion capture
JPH08155041A (ja) * 1994-12-05 1996-06-18 Advance Co Ltd イオントフォレシス用新規高能率電極システム
EP1762268A1 (de) * 1995-09-29 2007-03-14 Vyteris, Inc. Preisgünstige Elektroden für ein Iontophoresegerät
JP3459724B2 (ja) 1996-03-17 2003-10-27 久光製薬株式会社 イオントフォレーシス用電極デバイス
JP2009505805A (ja) * 2005-08-31 2009-02-12 アルザ・コーポレーシヨン アニオン性薬剤を電気的輸送送達するための陰極
EP2285362B1 (de) * 2008-06-19 2017-08-09 LTS LOHMANN Therapie-Systeme AG Zusammensetzung zur transdermalen verabreichung kationischer wirkstoffe
EP4368236A1 (de) * 2022-11-11 2024-05-15 Cambridge Enterprise Limited Iontophoretische vorrichtung zur verabreichung von medikamenten

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3964477A (en) * 1975-01-30 1976-06-22 Sybron Corporation Method of using electrodes having antiseptic properties for LIDC therapy
US4416274A (en) * 1981-02-23 1983-11-22 Motion Control, Inc. Ion mobility limiting iontophoretic bioelectrode
JPS5810066A (ja) * 1981-07-10 1983-01-20 株式会社アドバンス イオントフオレ−ゼ用プラスタ−構造体
CA1203286A (en) * 1982-06-16 1986-04-15 Minnesota Mining And Manufacturing Company Bioelectrode

Also Published As

Publication number Publication date
JPS61149168A (ja) 1986-07-07
JP2584438B2 (ja) 1997-02-26
EP0182520A2 (de) 1986-05-28
EP0182520B1 (de) 1992-03-25
CA1267937A (en) 1990-04-17
DE3585722D1 (de) 1992-04-30
EP0182520A3 (en) 1987-09-02

Similar Documents

Publication Publication Date Title
US4744787A (en) Iontophoresis apparatus and methods of producing same
US4747819A (en) Iontophoretic drug delivery
US5135477A (en) Iontophoretic drug delivery
EP0182520B2 (de) Gerät zur iontophoretischen Verabreichung von Medikamenten
US5395310A (en) Iontophoresis electrode
US5084008A (en) Iontophoresis electrode
US5057072A (en) Iontophoresis electrode
US7398121B2 (en) Iontophoresis device
EP1115454B1 (de) Gesteuerte medikamentdosierungsvorrichtung
US5320731A (en) Iontophoresis device for transcutaneous administration of a given total quantity of an active principle to a subject
JPH09511664A (ja) 薬物投与を強化した電気的移送系
JP2003519541A (ja) 競合イオンを用いた選択的薬剤送達プロフィル
US5766144A (en) High efficiency electrode system for iontophoresis
EP0429552B1 (de) Iontophorese Elektrode
WO1997012644A1 (en) Improved iontophoretic reservoir apparatus
Phipps et al. IONTOPHORETIC DRUG DELIVERY: ADVANTAGES AND LIMITATIONS

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): DE FR GB NL

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Kind code of ref document: A3

Designated state(s): DE FR GB NL

17P Request for examination filed

Effective date: 19880224

17Q First examination report despatched

Effective date: 19901120

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): DE FR GB NL

REF Corresponds to:

Ref document number: 3585722

Country of ref document: DE

Date of ref document: 19920430

ET Fr: translation filed
PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

26 Opposition filed

Opponent name: ALZA CORPORATION

Effective date: 19921221

Opponent name: SOCIETE NATIONALE ELF AQUITAINE

Effective date: 19921218

Opponent name: BECTON, DICKINSON AND COMPANY

Effective date: 19921214

NLR1 Nl: opposition has been filed with the epo

Opponent name: ALZA CORPORATION

Opponent name: SOCIETE NATIONALE ELF AQUITAINE

Opponent name: BECTON, DICKINSON AND COMPANY.

REG Reference to a national code

Ref country code: GB

Ref legal event code: 732E

RAP2 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: ALZA CORPORATION

NLS Nl: assignments of ep-patents

Owner name: ALZA CORPORATION TE PALO ALTO, CALIFORNIE, VER. ST

REG Reference to a national code

Ref country code: FR

Ref legal event code: TP

PLBQ Unpublished change to opponent data

Free format text: ORIGINAL CODE: EPIDOS OPPO

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: BECTON, DICKINSON AND COMPANY * 921218 SOCIETE NAT

Effective date: 19921214

NLR1 Nl: opposition has been filed with the epo

Opponent name: ALZA CORPORATION

Opponent name: SOCIETE NATIONALE ELF AQUITAINE

Opponent name: BECTON, DICKINSON AND COMPANY

RDAH Patent revoked

Free format text: ORIGINAL CODE: EPIDOS REVO

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

APAE Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOS REFNO

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

PLBQ Unpublished change to opponent data

Free format text: ORIGINAL CODE: EPIDOS OPPO

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

R26 Opposition filed (corrected)

Opponent name: BECTON, DICKINSON AND COMPANY * 19921218 SOCIETE N

Effective date: 19921214

REG Reference to a national code

Ref country code: GB

Ref legal event code: IF02

PLAW Interlocutory decision in opposition

Free format text: ORIGINAL CODE: EPIDOS IDOP

R26 Opposition filed (corrected)

Opponent name: VYTERIS INC. * 19921218 SOCIETE NATIONALE ELF AQUI

Effective date: 19921214

NLR1 Nl: opposition has been filed with the epo

Opponent name: VYTERIS INC.

Opponent name: ALZA CORPORATION

Opponent name: SOCIETE NATIONALE ELF AQUITAINE

Opponent name: BECTON, DICKINSON AND COMPANY

PUAH Patent maintained in amended form

Free format text: ORIGINAL CODE: 0009272

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: PATENT MAINTAINED AS AMENDED

27A Patent maintained in amended form

Effective date: 20020828

AK Designated contracting states

Kind code of ref document: B2

Designated state(s): DE FR GB NL

NLR2 Nl: decision of opposition
NLR3 Nl: receipt of modified translations in the netherlands language after an opposition procedure
ET3 Fr: translation filed ** decision concerning opposition
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20041003

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20041008

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20041021

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20041027

Year of fee payment: 20

APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20051027

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20051028

REG Reference to a national code

Ref country code: GB

Ref legal event code: PE20

NLV7 Nl: ceased due to reaching the maximum lifetime of a patent

Effective date: 20051028